Mechanisms Of Apoptosis And Extracellular Matrix Remodeling In Cervical Carcinoma

Purpose: To explore mechanisms of apoptosis in cervical squamous cell carcinoma, and the relationship between cervical extracellular matrix (ECM) remodling and the invasive of cervical squamous cell carcinoma. Methods: Immunohistochemical observations including TDT/dUTP nick end labeling (TUNEL) method, and Dual fluorescent labeling techniques were performed on cervical normal and squamous cell carcinoma tissue to detect PCNA, apoptosis and interrelated proteins caspase-3, caspase-8, Fas, FasL, Bax and Bcl-2, and type I, III and IV collagen, fibronectine, laminin, MMP-l, MMP-2, MT1-MMP, TIMP-2 expression in formalin-fixed, paraffin embedded cervical normal and squamous cell carcinoma tissue. The fluorescent results were detected by a confocal laser scanning microscopy. Results: The PCNA, apoptosis and caspase-3, Fas, FasL protein expressed in each case, and the distribution of positive cells was related each to other. immunoreactivity (IR) for Bax Fas, FasL and caspase-3 increased considerably in the cervical carcinoma tissue. Daul positive staining for apoptosis and caspase-3, Bax or Fas was appeared in some cells. No JR for caspase-8 and Bcl-2 was observed in cervical normal and tumor tissue. The subepithelial and vessel basement membrane staining of FN, LN and collagen IV revealed positive staining in normal cervical tissue, and the tense expression of type I and III collagen appeared in the ECM. In the cervical squamous cell carcinoma cases, three types collagen was decreased. The structure of type I and III collagen was scatters and the staining for collagen IV showed discontinuity, fragmentation or absence of basement membrane in the vicinity of cervical carcinoma, particularly in low-grade invasive carcinomas. The JR for LN, FN, MMP-1, MIMP-2 and MT1-MMIP increased, particularly in low-grade invasive carcinoma. In contrast, the JR for TIMP-2 was decreased as compare with high-grade carcinoma. 5 ~j~f 11 ~ Conclusion:.The apoptosis appeared in cervical normal and squamous cell carcinoma tissue, and the apoptotic mechanism of different kind of cells is different in one tissue The casapse-3, Fas/FasL and increase of BaxIBcl-2 take pert in regulation of apoptosis. In the cervical squamous cell carcinoma cases, the remodeling of ECM and collagen related with the activity of MMPs.